Health Topics

Post-exposure prophylaxis (PEP)

Post-exposure prophylaxis (PEP) is a special course of HIV treatment that aims to prevent people from becoming infected with HIV. PEP is prescribed, in some instances, to people who have potentially been exposed to the virus. The treatment, which can be accessed from clinics and health centres in many parts of the world, can prevent the virus from becoming established in the body of someone who has been exposed. PEP is particularly important for people who have been sexually assaulted or people who have been exposed to blood through a needle injury or other accident at work.

How does post-exposure prophylaxis (PEP) work?

Post-exposure prophylaxis is antiretroviral drug treatment that is started immediately after someone is exposed to HIV. The aim is to allow a person’s immune system a chance to provide protection against the virus and to prevent HIV from becoming established in someone’s body. It usually consists of a month long course of two or three different types of the antiretroviral drugs that are also prescribed as treatment for people living with HIV. The World Health Organisation recommends prescribing zidovudine and lamivudine as the preferred regimen, stating that countries are generally advised to use the same regimens as they would for treating HIV.

Post-exposure prophylaxis is part of a growing trend in using antiretroviral medicine as a preventative measure, along with pre-exposure prophylaxis and treatment as prevention.

Effectiveness of PEP

Post-exposure prophylaxis has been studied in human trials (see below). The cumulative evidence is enough to suggest that PEP might be effective in reducing the risk of HIV infection. This conclusion is widely recognised and as a result, a number of countries have produced guidelines suggesting the possible use of post-exposure prophylaxis in both occupational circumstances (for example a health-care worker who has been exposed in a hospital) and non-occupational circumstances (for example a person who has had unprotected sex). They tend to suggest that, as it is not 100 percent effective, post-exposure prophylaxis should only be used as a very last resort.

In cases where PEP is used, there are various factors that can affect its effectiveness.

Delayed initiation: In order for post-exposure prophylaxis to have a chance of working, the medication needs to be taken as soon as possible, and within 72 hours of exposure to HIV. Left any longer and it is thought that the effectiveness of the treatment is severely diminished. • Resistant virus: The person who potentially transmitted HIV (the ‘source’) may have a drug-resistant HIV virus, which could make PEP ineffective. • Adherence: It is very important that a person using PEP takes the treatment exactly as prescribed by their doctor or health worker. The side effects of the medication are a reason why some people find it difficult to adhere to the full 28-day course of treatment properly.

Who can benefit from post-exposure prophylaxis?

People exposed to blood or bodily fluids at work: Globally, it is a common occurrence for people to be exposed to blood or bodily fluids in occupational circumstances, particularly for health care workers. The World Health Organisation recommends that PEP be made available as much as possible for this group. • Victims of rape or sexual assault: PEP is especially important for children who have been sexually assaulted, as they could be particularly vulnerable to skin tearing that comes with aggravated sexual intercourse. It has been found that there are often low rates of adherence to PEP among victims of sexual assault, potentially due to stigma, trauma following rape and assault, treatment side effects and a lack of support. WHO recommends that PEP be made available as much as possible for this group. • People who may have been exposed to HIV through consensual sexual contact: PEP may be recommended if it is known that the sexual partner has HIV. Otherwise, it is often not recommended, as risks may outweigh the benefits. This can vary depending on the setting, or whether the sexual partner is from a ‘high-risk group’. PEP would rarely be recommended in cases of non-penetrative sex. • People potentially exposed through needles: For people who have shared needle equipment, if it is known that the other person who used the needle has HIV then PEP may be recommended. For people who have had a needlestick injury from a discarded needle outside of a healthcare setting, PEP is not usually recommended, because the virus cannot survive long outside of the human body so it is very unlikely that the needle could infect somebody.

Risks and side-effects

As with most antiretrovirals, post-exposure prophylaxis can cause side effects such as diarrhoea, headaches, nausea / vomiting and fatigue. Some of these side effects can be quite severe and it is estimated that 1 in 5 people give up the treatment before completion.

Cost-effectiveness of PEP

The question of who should receive PEP has proved to be quite controversial. Several cost-benefit analyses have revealed that providing PEP to all non-occupational exposures is not an economically efficient use of limited HIV treatment resources. Making PEP available appears to be cost-effective only when the patient has engaged in unprotected receptive anal intercourse or when the patient knows the HIV status of the partner. However, the demand for PEP does not always reflect cost-effectiveness. A ten year review of non-occupational PEP requests recorded at a Swiss clinic found an 850 percent increase in the number of people requesting PEP in the ten-year period and 58 percent of requests were for heterosexual exposure. Due to its potential benefit, there is also a strong human-rights based case for prescribing PEP.

The science, trials and development of PEP

Human trials of post-exposure prophylaxis

A number of small-scale studies have investigated the efficacy of post-exposure prophylaxis in humans by looking at occupational exposures to HIV. Health care workers tend to be at a slightly higher risk of being infected with HIV due to the nature of their work (although this risk is still very low). The most frequent exposures to HIV-infected blood in the occupational setting are caused by needle stick injuries or cuts with sharp objects. Zidovudine is the drug that is primarily prescribed after an occupational exposure to HIV and it is the only drug that has been tested in trials on health care workers. Nowadays most treatment starter packs contain a combination of zidovudine, lamivudine and nelfinavir, as it is generally thought that combination drug therapy is more effective than zidovudine alone.

The results of one occupational exposure study showed that taking a course of zidovudine after exposure reduced the risk of HIV infection by approximately 81 percent. These results cannot be taken as absolute, especially when there have been at least 13 reported cases where PEP has failed in health care workers worldwide. For some of these cases there was no plausible explanation for why PEP might have failed and therefore PEP cannot be considered as 100 percent effective.

One study enrolled 891 people who had requested post-exposure prophylaxis after possible non-occupational HIV exposure (e.g. sexual exposure or injecting drug use). The participants were all provided with a 28-day course of various combinations of zidovudine, lamivudine, stavudine and didanosine. Six out of the 700 that returned for testing after 12 weeks were HIV positive. However all 6 had had possible HIV exposures up to 6 months before commencing PEP. Therefore it was very difficult to determine the exact moment of exposure and whether PEP had been successful or not. There is a distinct lack of definitive evidence to show that PEP can be effective in non-occupational settings. Studies have generally concluded that PEP ‘might’ reduce the risk of HIV infection, but none have been able to say that it is a definite preventative.

Other observational evidence has been gathered from studies of survivors of sexual assault. In a South African study of 480 rape survivors taking a 6-week course of zidovudine and lamivudine, only one woman became HIV-positive. Another study looked at 2,000 non-occupational exposures to HIV from four countries (Australia, France, Switzerland, and the United States). Out of 350 people treated with PEP who reported being exposed to HIV-infected sources, none became infected as a result of PEP failure.

Is there a future for PEP?

Post-exposure prophylaxis is not going to be enough to significantly reduce the worldwide spread of HIV. It is a short-term preventative measure that is used as an ‘emergency’ precaution. PEP is considered as the very last resort in HIV prevention and should only be used when all other methods of HIV prevention have failed. However, with increasing widespread availability and further awareness, PEP can offer more people a way to reduce the risk of HIV infection, especially in cases of sexual assault or where the status of the partner is known.